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6-Methoxymellein Isolated from Carrot (Daucus carota L.) Targets Breast Cancer Stem Cells by Regulating NF-κB Signaling
Molecules ( IF 4.2 ) Pub Date : 2020-09-23 , DOI: 10.3390/molecules25194374
Ren Liu , Hack Sun Choi , Su-Lim Kim , Ji-Hyang Kim , Bong-Sik Yun , Dong-Sun Lee

The presence of breast cancer stem cells (BCSCs) induces the aggressive progression and recurrence of breast cancer. These cells are drug resistant, have the capacity to self-renew and differentiate and are involved in recurrence and metastasis, suggesting that targeting BCSCs may improve treatment efficacy. In this report, methanol extracts of carrot root were purified by means of silica gel, Sephadex LH-20, and preparative high-performance liquid chromatography to isolate a compound targeting mammosphere formation. We isolated the compound 6-methoxymellein, which inhibits the proliferation and migration of breast cancer cells, reduces mammosphere growth, decreases the proportion of CD44+/CD24- cells in breast cancer cells and decreases the expression of stemness-associated proteins c-Myc, Sox-2 and Oct4. 6-Methoxymellein reduces the nuclear localization of nuclear factor-κB (NF-κB) subunit p65 and p50. Subsequently, 6-methoxymellein decreases the mRNA transcription and secretion of IL-6 and IL-8. Our data suggest that 6-methoxymellein may be an anticancer agent that inhibits BCSCs via NF-κB/IL-6 and IL-8 regulation.

中文翻译:

从胡萝卜 (Daucus carota L.) 中分离的 6-Methoxymellein 通过调节 NF-κB 信号传导靶向乳腺癌干细胞

乳腺癌干细胞 (BCSC) 的存在会诱导乳腺癌的侵袭性进展和复发。这些细胞具有抗药性,具有自我更新和分化的能力,并参与复发和转移,表明靶向 BCSC 可能会提高治疗效果。在本报告中,胡萝卜根的甲醇提取物通过硅胶、Sephadex LH-20 和制备型高效液相色谱法纯化,以分离出靶向乳腺球形成的化合物。我们分离出化合物6-甲氧基蜜蜡,它抑制乳腺癌细胞的增殖和迁移,减少乳腺球生长,降低乳腺癌细胞中CD44+/CD24-细胞的比例,并降低干细胞相关蛋白c-Myc、Sox的表达-2 和 Oct4。6-Methoxymellein 降低核因子-κB (NF-κB) 亚基 p65 和 p50 的核定位。随后,6-甲氧基蜜蜡降低了 IL-6 和 IL-8 的 mRNA 转录和分泌。我们的数据表明,6-甲氧基蜜蜡可能是一种通过 NF-κB/IL-6 和 IL-8 调节抑制 BCSCs 的抗癌剂。
更新日期:2020-09-23
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